Fatty liver disease (FLD, also know as hepatosteatosis) is a prevalent liver condition that occurs when lipids accumulate in liver cells. The lipid accumulation causes cellular injury and sensitizes the liver to further injuries. The accumulated lipids may also impair hepatic microvascular circulation.
FLD may arise from a number of sources, including excessive alcohol consumption and metabolic disorders, such as those associated with insulin resistance, obesity, and hypertension. Nonalcoholic fatty liver disease (NAFLD) may also result from metabolic disorders such as, e.g., galactosemia, glycogen storage diseases, homocystinuria, and tyrosemia, as well as dietary conditions such as malnutrition, total parenteral nutrition, starvation, and overnutrition. In certain cases, NAFLD is associated with jejunal bypass surgery. Other causes include exposure to certain chemicals such as, e.g., hydrocarbon solvents, and certain medications, such as, e.g., amiodarone, corticosteroids, estrogens (e.g., synthetic estrogens), tamoxifen, maleate, methotrexate, nucleoside analogs, and perhexiline. Acute fatty liver conditions can also arise during pregnancy.
FLD is a prevalent condition. NAFLD alone has been estimated to affect as much as 25-33% of the adult population in the developed world. See, e.g., Cortez-Pinto et al., J. Am. Med. Assoc. 282:1659-1664 (1999); Adams et al., Can. Med. Assoc. J. 172:899-905 (2005); and Clark et al., J. Am. Med. Assoc. 289:3000-3004 (2003). Moreover, NAFLD is also believed to affect as many as 3-10% of obese children.
FLD can progress to more advanced liver disease such as nonalcoholic steatohepatitis (NASH; metabolic steatohepatitis), a condition characterized by liver inflammation and damage, often accompanied by fibrosis or cirrhosis of the liver. NASH may progress to further liver damage ultimately leading to chronic liver failure and, in some cases, hepatocellular carcinoma.
NASH has a prevalence of up to 9% of the general population. See, e.g., Cortez-Pinto et al., J. Am. Med. Assoc. 282:1659-1664 (1999). NASH patients have an increased incidence of liver-related mortality. Adams et al., Can. Med. Assoc. J. 172:899-905 (2005). About 640,000 adults in the U.S. are estimated to have cirrhosis resulting from NAFLD. Clark et al., J. Am. Med. Assoc. 289:3000-3004 (2003). This number may underestimate the actual incidence, as undetected NAFLD is believed to be an important cause of cryptogenic liver cirrhosis. See, e.g., Clark et al., J. Am. Med. Assoc. 289:3000-3004 (2003) and Adams et al., Can. Med. Assoc. J. 172:899-905 (2005).
There are no treatments for NAFLD whose efficacy has been demonstrated by large-scale rigorous clinical trials. In general, NAFLD patients are advised to exercise, lose weight, and avoid hepatotoxins. Other experimental therapies include antioxidants, cytoprotective agents, antidiabetic agents, insulin-sensitizing agents, and anti-hyperlipidemic agents. See, e.g., Clark et al., J. Am. Med. Assoc. 289:3000-3004 (2003) and Adams et al., Can. Med. Assoc. J. 172:899-905 (2005).
In view of the high prevalence of disorders associated with hepatic lipid deposits, the severity of these conditions, and the lack of proven treatments, it is important to develop new treatments for such conditions.